Safety and immune response to a challenge dose of hepatitis B vaccine in healthy children primed 10years earlier with hexavalent vaccines in a 3, 5, 11-month schedule: An open-label, controlled, multicentre trial in Italy

Vaccine. 2017 Jul 13;35(32):4034-4040. doi: 10.1016/j.vaccine.2017.05.047. Epub 2017 Jun 16.

Abstract

Background and aims: The strategy of vaccinating infants to prevent hepatitis B virus infection in adolescence or adulthood requires durable immunity. This study investigated responses to a challenge dose of monovalent hepatitis B vaccine in children primed with three doses of either Hexavac® or Infanrix hexa® 10years earlier during infancy.

Methods: This open-label, controlled, multicentre study conducted in Italy, enrolled 751 healthy pre-adolescents (aged 11-13years) who were given either Hexavac (n=409) or Infanrix hexa (n=342) at 3, 5 and 11months of life. All participants received a challenge dose of a monovalent hepatitis B vaccine (HBVaxPro® 5µg). The concentrations of antibodies to hepatitis B surface antigen (anti-HBs) were measured before and 1month after the challenge dose. The analysis was descriptive and no formal hypothesis was tested.

Results: One month post-challenge, 331 participants in the Hexavac cohort [83.6%, 95% CI: 79.6; 87.1] and 324 in the Infanrix hexa cohort [96.4%, 95% CI: 93.8; 98.1] had anti-HBs concentrations ≥10mIU/mL. Before the challenge dose, an anti-HBs concentration of ≥10mIU/mL was found in 94 children in the Hexavac cohort [23.9%, 95% CI: 19.7; 28.4] and in 232 children in the Infanrix hexa cohort [69%, 95% CI: 63.8; 74.0]. Among children with a pre-challenge anti-HBs concentration of <10mIU/mL, 236 [78.7%, 95% CI: 73.6; 83.2] in the Hexavac cohort and 92 [88.5%, 95% CI: 80.7; 93.9] in the Infanrix hexa cohort achieved protective anti-HBs antibody concentrations. No evidence of active hepatitis B disease was observed in either group, and the HBVaxPro challenge dose was well tolerated.

Conclusions: These data confirm that immune memory persists in a high percentage of children (>80%) at least 10years after a two-dose primary and booster vaccination schedule with a hexavalent vaccine (Hexavac or Infanrix hexa).

Trial registration: EudraCT Number: 2013-001602-28; clinicaltrials.gov: NCT02012998.

Keywords: Challenge dose; Hepatitis B; Hexavalent vaccine; Immune memory; Vaccinated children.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects*
  • Diphtheria-Tetanus-Pertussis Vaccine / immunology*
  • Female
  • Haemophilus Vaccines / administration & dosage
  • Haemophilus Vaccines / adverse effects*
  • Haemophilus Vaccines / immunology*
  • Healthy Volunteers
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / adverse effects*
  • Hepatitis B Vaccines / immunology*
  • Humans
  • Immunization Schedule*
  • Immunologic Memory*
  • Infant
  • Italy
  • Male
  • Poliovirus Vaccine, Inactivated / administration & dosage
  • Poliovirus Vaccine, Inactivated / adverse effects*
  • Poliovirus Vaccine, Inactivated / immunology*
  • Time Factors
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / adverse effects
  • Vaccines, Combined / immunology

Substances

  • Diphtheria-Tetanus-Pertussis Vaccine
  • Haemophilus Vaccines
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Hexavac
  • Poliovirus Vaccine, Inactivated
  • Vaccines, Combined
  • diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine

Associated data

  • EudraCT/2013-001602-28
  • ClinicalTrials.gov/NCT02012998